EXPERIMENTS SUGGESTING A ROLE FOR NITRIC-OXIDE IN THE HIPPOCAMPUS IN MEMORY PROCESSES

Nitric oxide (NO) has been proposed to be involved in the induction of long-term potentiation (LTP) and in other processes. When coupled wit h weak tetanic stimulation, NO produces a long-term synaptic enhanceme nt on its own. N-Nitroarginine (NO-Arg) inhibits NO-synthase, the enzy me that produces NO, and blocks LTP in hippocampal slices. We investig ated the effect on memory of the pre- or post-training infusion of NO- Arg and of the post-training infusion of the NO donor, S-nitroso-N-ace tylpenicillamine (SNAP) into the hippocampus. Male Wistar rats were im planted bilaterally with cannulae in the dorsal hippocampus. After rec overy from surgery, the animals were trained in step-down inhibitory a voidance using a 0.4-mA footshock and tested for retention 24 h later. NO-Arg (2.0 mu g) hindered retention test performance when infused ei ther before or immediately after training, but not 30 or 60 min later. SNAP (5.0 mu g) enhanced retention test performance when given 0, 60, or 150 min, but not 300 min, after training. The results suggest that memory storage depends on NO-sensitive processes in the hippocampus, perhaps, as suggested in previous papers, LTP generated at the time of training. (C) 1995 Academic Press, Inc.